1. Field of the Invention
The present invention concerns novel Neuropeptide Y analogs, pharmaceutical formulations containing the same, and methods of lowering blood pressure and inducing satiety in a subject employing the same.
2. Description of the Background
Neuropeptide Y is a 36 amino acid member of the pancreated polypeptide family. It is highly concentrated in both the central and peripheral mammalian nervous system. It apparently serves important functions in the control of blood pressure, satiety, and other responses. The amino acid sequence of Neuropeptide Y is known. See, e.g., K. Tatemoto, Proc. Natl. Acad. Sci. USA 79, 5485-5489 (1982).
Neuropeptide Y analogs are disclosed in U.S. Pat. No. 5,026,685 to Boublik et al. The compounds are indicated to be active in lowering the blood pressure of mammalian subjects. The compounds are indicated to be 18-20 amino acids in length, and include amino acid residues 19 to 36 of human NPY (see, e.g., Column 2, lines 25-35 therein). Additional Neuropeptide Y analogs are disclosed in U.S. Pat. No. 5,328,899 to Boublik et al.
A recent study proposed two modified fragments of NPY, called PYX.sub.1 and PYX.sub.2, to be specific NPY receptor antagonists. Both compounds are analogs of the 27-36 residue C-terminal fragment. Both compounds have a D-amino acid substitution at Thr.sup.32. [3-(2,6-dichlorobenzyl)] is substituted at Tyr.sup.27 on PYX.sub.1, and is substituted at both Tyr.sup.27 and Tyr.sup.36 in PYX.sub.2. See K. Tatemoto, Ann. NY Acad. Sci. 611, 1-6 (1990); K. Tatemoto et al., Proc. Natl. Acad. Sci. USA 89, 1174-1178 (1992).